Cited by 343Virology and Viral DiseasesAnimal Virus Infections StudiesGenomics and Phylogenetic Studies

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Viral Nucleic Acids in Live-Attenuated Vaccines: Detection of Minority Variants and an Adventitious Virus

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Victoria, Joseph G., Wang, Chunlin, Jones, Morris S., Jaing, Crystal, McLoughlin, Kevin, Gardner, Shea, Delwart, Eric L.·2010·Journal of Virology

DOI 10.1128/jvi.02690-09PMC PMC2876658

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Abstract

Metagenomics and a panmicrobial microarray were used to examine eight live-attenuated viral vaccines. Viral nucleic acids in trivalent oral poliovirus (OPV), rubella, measles, yellow fever, varicella-zoster, multivalent measles/mumps/rubella, and two rotavirus live vaccines were partially purified, randomly amplified, and pyrosequenced. Over half a million sequence reads were generated covering from 20 to 99% of the attenuated viral genomes at depths reaching up to 8,000 reads per nucleotides. Mutations and minority variants, relative to vaccine strains, not known to affect attenuation were detected in OPV, mumps virus, and varicella-zoster virus. The anticipated detection of endogenous retroviral sequences from the producer avian and primate cells was confirmed. Avian leukosis virus (ALV), previously shown to be noninfectious for humans, was present as RNA in viral particles, while simian retrovirus (SRV) was present as genetically defective DNA. Rotarix, an orally administered rotavirus vaccine, contained porcine circovirus-1 (PCV1), a highly prevalent nonpathogenic pig virus, which has not been shown to be infectious in humans. Hybridization of vaccine nucleic acids to a panmicrobial microarray confirmed the presence of endogenous retroviral and PCV1 nucleic acids. Deep sequencing and microarrays can therefore detect attenuated virus sequence changes, minority variants, and adventitious viruses and help maintain the current safety record of live-attenuated viral vaccines.

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Authors: Victoria, J. G., Wang, C., Jones, M. S., Jaing, C., McLoughlin, K., Gardner, S., & Delwart, E. L.
Affiliations: University of California, San Francisco (US)
Stanford University (US)
David Grant USAF Medical Center (US)
Lawrence Livermore National Laboratory (US)
ORCID: Wang, Chunlin
Jones, Morris S.
Jaing, Crystal
McLoughlin, Kevin
Delwart, Eric L.
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2010-06-15
Volume: 84
Issue: 12
Pages: 6033-6040
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.02690-09
PMC: PMC2876658
OpenAlex: W2106638291
Cited by: 342
References: 38
Citations by year: 2026: 5 · 2025: 13 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 13 · 2020: 17 · 2019: 17 · 2018: 22 · 2017: 18 · 2016: 25 · 2015: 19 · 2014: 48 · 2013: 29 · 2012: 23
FWCI: 27.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Energy (DEAC5207NA27344, AC52‐07NA27344)
Blood Systems Research Institute (R01HL083254)
Sanjay Gandhi Postgraduate Institute of Medical Sciences
U.S. Air Force
National Heart, Lung, and Blood Institute (R01HL083254)
Air Force Surgeon General
Lawrence Livermore National Laboratory (DE‐AC5207NA27344, 02-SI-008, AC52-07NA27344)
Topics: Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords: live attenuated vaccine, viral nucleic acids, minority variants, adventitious viruses, oral polio vaccine, rubella vaccine, measles vaccine, yellow fever vaccine, varicella-zoster vaccine, mumps vaccine, rotavirus vaccine, Rotarix, porcine circovirus type 1, endogenous retroviruses, avian leukosis virus, simian retroviruses, vaccine safety, metagenomics
MeSH terms: Animals, DNA, Viral, Humans, Molecular Sequence Data, Phylogeny, Vaccines, Attenuated, Genetic Variation, Viral Vaccines, Virus Diseases, Viruses, Genome, Viral, Sequence Analysis, DNA

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Viral Nucleic Acids in Live-Attenuated Vaccines: Detection of Minority Variants and an Adventitious Virus

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